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Biomedical subjects

D Lundberg

Publications and source records attributed to D Lundberg.

At least 73 records · Page 4Linked to original sources
PubMed1981

Central respiratory stimulant effect by thyrotropin in releasing hormone in the rat.

Anaesthetized male rats were injected intracerebroventricularly with the tripeptide, thyrotropin releasing hormone (TRH). Respiratory frequency (f), tidal volume (VT) and minute volume (VE) were measured in a closed whole body plethysmograph by a low pressure transducer connected to a Grass polygraph. TRH induced an approximately 50% increase in f, while VT was not altered. VE increased in the same proportion as f. Our results indicate that TRH neurons or TRH-sensitive receptors may be involved in the regulation of central respiratory activity.

Animals↗
PubMed1981

GABA-ergic mechanisms in central respiratory control in the anesthetized rat.

Rats lightly anesthetized with halothane were injected intracerebroventricularly (i.c.v.) with gamma aminobutyric acid (GABA) and the GABA-like drugs muscimol, baclofen, and gamma-hydroxybutyric acid (GHBA). Respiratory frequency (f) was reduced after GABA (1 mg) but increased after baclofen (0.5 microgram), while muscimol (0.5 microgram) or GHBA (1 mg) did no affect f. However, GHBA administered repeatedly caused a dose-dependent increase in f. Tidal volume (VT) decreased in a dose-dependent fashion after i.c.v. administration of all the drugs used. Taken together, these changes in f and VT resulted mainly in a dose dependent decrease in minute volume (VE) after GABA and muscimol while after baclofen and GHBA VE was increased due to the marked stimulation of f after repeated administration. Mean arterial pressure (MAP) decreased after GABA and muscimol while no effect or a slight increase was seen after baclofen and GHBA. Heart rate (HR) was unaltered after muscimol, decreased after gaba but slightly increased after GHBA and baclofen. No alterations were seen in blood gases except after administration of GABA which induced a slight hypoxia, hypercapnia and acidosis. The data indicate that an activation of GABA-ergic mechanisms results in a respiratory depression. Moreover, the effects of GABA and muscimol are probably due to a direct GABA-ergic receptor activation while the effects elicited by baclofen and GHBA are due to other mechanisms than direct GABA receptor activation or indirect effects via other system on respiratory regulating centers.

Animals↗
PubMed1981

Vascular and metabolic effects of methylprednisolone and phenoxybenzamine during controlled hypotension in the dog.

The relationship between central haemodynamics and vascular and metabolic parameters in skeletal muscle was studied in dogs subjected to controlled haemorrhagic hypotension and treated with cumulative doses of methylprednisolone (4-32 mg x kg-1), (or saline in the control group), followed by phenoxybenzamine. There were no significant haemodynamic or metabolic changes between the groups during the injections of steroid or saline. The alpha-adrenergic receptor blockade caused, as found earlier, a pronounced vasodilation in the steroid group, which was parallelled by an increase in muscle blood flow in the same order of magnitude. There was no clearcut relationship between metabolic and vascular effects in the groups. Despite the significant difference in blood flow between the groups after phenoxybenzamine, only small and insignificant differences were seen in muscle metabolites, with the exception of muscle lactate which showed higher values in the steroid group. The study provides further evidence in support of the hypothesis that the haemodynamic effects of the combination of methylprednisolone and phenoxybenzamine are of neurogenic origin.

Animals↗
PubMed1981

Neuronal and extraneuronal uptake of 3H-noradrenaline in rat portal vein in vitro.

Rat portal veins were incubated with 3 different concentrations of 3H-l-noradrenaline (3H-l-NA) and the radioactive material retained in the tissue as well as that present in the postincubation medium was analyzed after a postincubation period in substrate-free medium. Inhibition of the neuronal amine uptake mechanism (by preincubation with LU 3-010) reduced the retention of radioactivity in the tissue more at low than at high substrate concentrations. At increasing substrate concentrations the relative role of the extraneuronal amine uptake was increased. Corticosterone and hydrocortisone reduced extraneuronal accumulation whereas betamethasone and methylprednisolone in the concentrations used were ineffective, indicating that the inhibition of extraneuronal uptake by the corticosteroids is unrelated to their glucocorticoid potency. When the composition of the retained radioactivity was analyzed, NA was found to be the major component of the retained radioactivity after inhibition of extraneuronal uptake, whereas tritiated catabolites were found to be the predominating constituent of the retained radioactivity after neuronal uptake inhibition. The possible role of inactivation of the adrenergic transmitter by the extraneuronal uptake mechanism in different situations is discussed.

Animals↗
PubMed1981

Transient apnea after an enkephalin analogue in the preterm rabbit.

FK 33-824, a potent enkephalin analogue was administered systemically, 0.5-5 mg/kg to preterm neonatal rabbits. A marked decrease in respiratory frequency as well as irregular breathing and apneic spells was recorded at 5 mg/kg. Tidal volume was not affected. The enkephalin-induced respiratory depression was restored immediately after naloxone (10 mg/kg). Bases on the results it may be speculated upon whether brain stem enkephalin neurons are involved in the pathogenesis of neonatal transient apnea and irregular breathing.

Animals↗
PubMed1980

Respiratory effects of gamma-hydroxybutyric acid in anesthetized rats.

Rats lightly anesthetized with halothane were treated with graded intraperitoneal doses of gamma-hydroxybutyric acid (GHBA), a GABA analogue. The drug induced a dose dependent decrease in minute ventilation, mainly due to reduced respiratory frequency. A reduced pH in arterial blood was recorded. GHBA also blunted or abolished the respiratory response to CO2 exposure in a dose-related way. Picrotoxin (0.25, 0.5 or 1.0 mg/kg intravenously), a presumed GABA antagonist did not significantly change the respiratory pattern when given alone but clearly antagonized the GHBA-induced respiratory depression. It is concluded that GABA-ergic mechanisms are involved in central respiratory control.

Anesthesia, General↗
PubMed1980

Evidence that respiratory depression by serotonin agonists may be exerted in the central nervous system.

Resting with CO2 stimulated respiration were measured by means of a whole body plethysmograph in rats lightly anesthetized with halothane. The respiratory effects of different doses of the serotonin precursor 5-HTP, and the serotonin agonist 5-methoxy-N,N-dimethyltryptamine were studied as well as the effects of a serotonin antagonist methysergide and p-chlorophenylalanine, an inhibitor of serotonin synthesis. The serotonergic agonists decreased tidal volume and minute volume in a dose dependent manner and produced a respiratory acidosis. The respiratory depressant effect was antagonized by methysergide, and the serotonergic antagonist and synthesis inhibitor alone stimulated respiration. Rats given intraventricular 5-methoxy-N,N-dimethyltryptamine also evidenced a decrease in tidal volume, and this response was greater in animals given 5,7-dihydroxytryptamine. It seems likely that CNS serotonin receptors are involved in the control of both basal and CO2 stimulated respiration.

5-Hydroxytryptophan↗
PubMed1980

Effects of hydrocortisone, phenoxybenzamine and propranolol on the blood plasma levels of adrenaline and noradrenaline during hemorrhagic hypotension in the dog.

The adrenergic aspects of the mechanism(s) of the vasodilating action of phenoxybenzamine and massive doses of hydrocortisone were studied in anesthetized dogs subjected to controlled hemorrhagic shock. During the predrug hypotension period with decreased cardiac output and heart rate, the plasma adrenaline and noradrenaline levels were both increased. Phenoxybenzamine injected alone augmented the cardiac output and heart rate and reduced the plasma adrenaline without changing the plasma noradrenaline concentration. However, if the adrenergic alpha-receptor blocker was administered in combination with massive doses of hydrocortisone, the degree of vasodilation increased further with a concomitant increase in the concentrations of the two plasma catecholamines. Thus there seems to be no clear-cut relationship between hemodynamic changes and plasma catecholamines. The present findings illustrate the extreme complexity of plasma catecholamine kinetics during hypovolemic shock.

Animals↗
PubMed1980

Effects of adrenergic neuron and ganglion blockers on hemodynamics and plasma catecholamine levels after corticosteroids during hemorrhagic shock in the dog.

The involvement of adrenergic mechanisms in the ability of massive doses of methylprednisolone to potentiate the vasodilatory effects of phenoxybenzamine during controlled hemorrhagic shock was investigated. Dogs were subjected to ligation of the adrenals and, with the exception of the controls, were pretreated with either hexamethonium or bretylium. Despite careful surgery, the adrenal ligation, per se, failed to alter the concentration of plasma catecholamines. Hexamethonium and bretylium, on the other hand, both decreased the levels of plasma catecholamines: noradrenaline to a greater extent than adrenaline. Methylprednisolone was almost ineffective after ganglionic or adrenergic neuron blockade. Furthermore, the degree of vasodilation after methylprednisolone and phenoxybenzamine seemed to correlate better with plasma noradrenaline than with adrenaline. These findings indicate that the ability of methylprednisolone to induce vasodilation in the presence of adrenergic alpha-receptor blockade in hypovolemic shock in the dog relies on an intact release of noradrenaline from postganglionic adrenergic nerve terminals.

Adrenal Medulla↗
PubMed1980

Effects of different monoamine oxidase inhibitors on respiratory activity in rats with chronically impaired central serotonergic function.

Resting and CO2 stimulated respiration were measured by means of a whole-body plethysmograph in rats lightly anaesthetized with halothane. Rats pretreated neonatally with intracisternal 5,7-dihydroxytryptamine (5,7-DHT) to destruct permanently central serotonergic neurones had significantly lower resting and CO2 stimulated respiratory frequency (RF) and minute volume (VM) than naive rats. In the 5,7-DHT pretreated rats, but not in naive rats, the monoamine oxidase inhibitors clorgyline and pargyline further reduced both resting and CO2 stimulated RF and VM, whereas 1-deprenyl stimulated respiration. The results provide additional evidence that monoaminergic mechanisms are involved in central modulation of respiration in which activation of a serotonergic neuronal system depresses, and dopaminergic activation stimulates respiration.

5,7-Dihydroxytryptamine↗
PubMed1980

Respiratory depression by GABA-ergic drugs in the preterm rabbit.

Respiratory parameters were studied in preterm rabbits (gestational age 29 days) after intraperitoneal administration of the GABA-like drugs gamma-hydroxybutyric acid and muscimol. The animals were anaesthetized with 0.7% halothane in oxygen and studied in a closed body plethysmograph. Both drugs induced a decreased respiratory frequency and minute volume. Tidal volume decreased after muscimol, but not after gamma-hydroxybutyric acid administration. The present results indicate that an increased GABA-ergic activity causes respiratory depression in the preterm neonatal rabbit, presumably by an action on central nervous frequency and tidal volume modulating systems. Central GABA neurons may thus be involved in the pathogenesis of neonatal respiratory depression and irregular breathing.

Animals↗
PubMed1979

Dopaminergic interaction with the respiratory control system in the rat.

Apomorphine given to rats lightly anesthetized with halothane produces a dose dependent increase in respiratory frequency and minute ventilation. Although basal arterial CO2 tensions were not significantly altered by apomorphine, the mechanical response to exogenous CO2 exposure was greatly increased in rats given apomorphine. Haloperidol returned the apomorphine-stimulated respiratory pattern to control values. It is concluded that dopamine neurons may have important interactions with respiratory control.

Animals↗
PubMed1978

The adrenergic mechanism of the haemodynamic effects of massive doses of hydrocortisone in controlled haemorrhagic shock in the dog.

Haemorrhagic shock was induced in anaesthetized dogs by bleeding them into a blood reservoir system. By adjusting the blood level of the reservoir at a certain distance over the heart level the mean arterial blood pressure was kept at 6.7 kPa (50 mmHg). As has been found earlier, massive doses of hydrocortisone (80-560 mg.kg-1 body weight) caused a dose-dependent decrease in the total peripheral resistance. The degree of vasodilation distinctly increased during concomitant alpha-receptor blockade induced by phenoxybenzamine. The beta-receptor blocking drug propranolol efficiently inhibited the vasodilation caused by hydrocortisone and phenoxybenzamine. The findings fit with the hypothesis that massive doses of hydrocortisone induce an increased stimulation of the adrenergic beta2-receptors of the vascular smooth muscles.

Adrenergic beta-Antagonists↗